Prognostic value of interleukin-1 beta [IL-1 beta] and tumor necrosis factor-a [TNF-alpha] in full-term newborns with hypoxic-ischemic encephalopathy

ABSTRACT

A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurological outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. The aim of this study was to examine the relation of plasma and cerebrospinal fluid [CSF] interleukin-1 beta [IL-1beta] and tumor necrosis factor-alpha [TNF-alpha] to the severity of hypoxic-ischemic encephalopathy [HIE] and to the neurological outcome in full-term newborns with HIE. Thirty full-term neonates with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life for determination of IL-1beta and TNF-alpha by ELISA. Five neonates died soon after the hypoxic insult. Neurological examination and Denver Developmental Screening Test [DDST] were performed at 12 months in the survivors. The results showed that, at the age of 12 months, neurological examination and DDST showed that 13 infants were normal; 12 had abnormal neurological findings and/or an abnormal DDST result. Thirteen normal infants were classified as group1 and 17 infants [12 with abnormal neurological findings and/or an abnormal DDST and five who died] as group 2. CSF IL-1beta and TNF-alpha levels in-group 2 were significantly higher than those in-group1 [P = 0.0005 for IL-1beta, and P = 0.003 for TNF-alpha]. Plasma IL-1beta and TNF-alpha levels were not significantly different between the two groups [P = 0.098 for IL-1 beta, and P= 0.275 for TNF-alpha. CSF IL-1 beta but not TNF-alpha levels, in-group 2 were even higher than those in-group1, although non-survivors were excluded from group 2 [P = 0.001 for IL-1beta, and P = 0.257 for TNF-alpha]. When the patients were evaluated according to the stages of Sarnat, the differences in the three groups were significant [P = 0.002 for IL-1beta, and P = 0.03 for TNF-alpha]. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha levels than the patients whose samples were taken after 6 hours [P = 0.0001 for IL-1 beta and P = 0.015 for TNF-alpha